Introduction: Mild-to-moderate hypertriglyceridemia (HTG) is commonly encountered and is associated with atherosclerotic cardiovascular disease (ASCVD). Elevated plasma triglyceride (TG) levels reflect high levels of triglyceride-rich lipoproteins, against which lipid-lowering therapies that reduce low-density lipoprotein cholesterol are relatively ineffective. Apolipoprotein (apo) C-III is a new pharmacological target to reduce triglycerides and potentially also cardiovascular disease risk.
Areas covered: Here, we evaluate current lipid-lowering therapies and their effect on TG levels; genetic, pre-clinical, cellular, molecular biology, and translational studies that emphasize the importance of apo C-III in the metabolism of TG-rich lipoproteins and ASCVD risk; and clinical trials of pharmacotherapies that reduce TG levels via apo C-III inhibition. The PubMed database was searched using terms: apolipoprotein C-III, ARO-APOC3, atherosclerotic cardiovascular disease, olezarsen, triglycerides, and volanesorsen; study types: clinical trials, systematic reviews, and meta-analyses; and time criterion 2005 to present.
Expert opinion: Apo C-III inhibition is a promising treatment approach for adults with mild-to-moderate HTG and either established atherosclerotic cardiovascular disease or its risk factors. Biologic agents such as volanesorsen, olezarsen, and ARO-APOC3 significantly reduce plasma levels of apo C-III and TG, although data on cardiovascular outcomes are lacking. Volanesorsen is associated with thrombocytopenia in patients with severe HTG, but other agents appear to be better tolerated. Clinical trials with long-term follow-up of cardiovascular outcomes will establish the validity of apo C-III inhibition.
Keywords: AROAPOC3; Antisense oligonucleotide; apolipoprotein C-III; atherosclerotic cardiovascular disease; olezarsen, RNA interference; triglycerides; volanesorsen.